CD36_MESAU
ID CD36_MESAU Reviewed; 472 AA.
AC P70110;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 25-MAY-2022, entry version 89.
DE RecName: Full=Platelet glycoprotein 4;
DE AltName: Full=Glycoprotein IIIb;
DE Short=GPIIIB;
DE AltName: Full=PAS IV;
DE AltName: Full=PAS-4;
DE AltName: Full=Platelet glycoprotein IV;
DE Short=GPIV;
DE AltName: CD_antigen=CD36;
GN Name=CD36;
OS Mesocricetus auratus (Golden hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Mesocricetus.
OX NCBI_TaxID=10036;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Huang X., Acton L.S., Penman M., Krieger M.;
RL Submitted (DEC-1995) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Multifunctional glycoprotein that acts as receptor for a
CC broad range of ligands. Ligands can be of proteinaceous nature like
CC thrombospondin, fibronectin, collagen or amyloid-beta as well as of
CC lipidic nature such as oxidized low-density lipoprotein (oxLDL),
CC anionic phospholipids, long-chain fatty acids and bacterial diacylated
CC lipopeptides. They are generally multivalent and can therefore engage
CC multiple receptors simultaneously, the resulting formation of CD36
CC clusters initiates signal transduction and internalization of receptor-
CC ligand complexes. The dependency on coreceptor signaling is strongly
CC ligand specific. Cellular responses to these ligands are involved in
CC angiogenesis, inflammatory response, fatty acid metabolism, taste and
CC dietary fat processing in the intestine (By similarity). Binds long-
CC chain fatty acids and facilitates their transport into cells, thus
CC participating in muscle lipid utilization, adipose energy storage, and
CC gut fat absorption (By similarity). Mechanistically, binding of fatty
CC acids activates downstream kinase LYN, which phosphorylates the
CC palmitoyltransferase ZDHHC5 and inactivates it resulting in the
CC subsequent depalmitoylation of CD36 and caveolar endocytosis (By
CC similarity). In the small intestine, plays a role in proximal
CC absorption of dietary fatty acid and cholesterol for optimal
CC chylomicron formation, possibly through the activation of MAPK1/3
CC (ERK1/2) signaling pathway (By similarity). Involved in oral fat
CC perception and preferences (By similarity). Detection into the tongue
CC of long-chain fatty acids leads to a rapid and sustained rise in flux
CC and protein content of pancreatobiliary secretions (By similarity). In
CC taste receptor cells, mediates the induction of an increase in
CC intracellular calcium levels by long-chain fatty acids, leading to the
CC activation of the gustatory neurons in the nucleus of the solitary
CC tract (By similarity). Important factor in both ventromedial
CC hypothalamus neuronal sensing of long-chain fatty acid and the
CC regulation of energy and glucose homeostasis (By similarity). Receptor
CC for thrombospondins, THBS1 and THBS2, mediating their antiangiogenic
CC effects (By similarity). As a coreceptor for TLR4:TLR6 heterodimer,
CC promotes inflammation in monocytes/macrophages. Upon ligand binding,
CC such as oxLDL or amyloid-beta 42, interacts with the heterodimer
CC TLR4:TLR6, the complex is internalized and triggers inflammatory
CC response, leading to NF-kappa-B-dependent production of CXCL1, CXCL2
CC and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via
CC TICAM1 signaling pathway, as well as IL1B secretion, through the
CC priming and activation of the NLRP3 inflammasome. Selective and
CC nonredundant sensor of microbial diacylated lipopeptide that signal via
CC TLR2:TLR6 heterodimer, this cluster triggers signaling from the cell
CC surface, leading to the NF-kappa-B-dependent production of TNF, via
CC MYD88 signaling pathway and subsequently is targeted to the Golgi in a
CC lipid-raft dependent pathway (By similarity).
CC {ECO:0000250|UniProtKB:P16671, ECO:0000250|UniProtKB:Q07969,
CC ECO:0000250|UniProtKB:Q08857}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=butanoate(out) = butanoate(in); Xref=Rhea:RHEA:45248,
CC ChEBI:CHEBI:17968; Evidence={ECO:0000250|UniProtKB:P16671};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45249;
CC Evidence={ECO:0000250|UniProtKB:P16671};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z)-octadecenoate(out) = (9Z)-octadecenoate(in);
CC Xref=Rhea:RHEA:33655, ChEBI:CHEBI:30823;
CC Evidence={ECO:0000250|UniProtKB:P16671};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33656;
CC Evidence={ECO:0000250|UniProtKB:P16671};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z)-octadecadienoate(out) = (9Z,12Z)-
CC octadecadienoate(in); Xref=Rhea:RHEA:45264, ChEBI:CHEBI:30245;
CC Evidence={ECO:0000250|UniProtKB:P16671};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45265;
CC Evidence={ECO:0000250|UniProtKB:P16671};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=tetradecanoate(out) = tetradecanoate(in);
CC Xref=Rhea:RHEA:45252, ChEBI:CHEBI:30807;
CC Evidence={ECO:0000250|UniProtKB:P16671};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45253;
CC Evidence={ECO:0000250|UniProtKB:P16671};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hexadecanoate(out) = hexadecanoate(in); Xref=Rhea:RHEA:45256,
CC ChEBI:CHEBI:7896; Evidence={ECO:0000250|UniProtKB:P16671};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45257;
CC Evidence={ECO:0000250|UniProtKB:P16671};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=tetracosanoate(out) = tetracosanoate(in);
CC Xref=Rhea:RHEA:45260, ChEBI:CHEBI:31014;
CC Evidence={ECO:0000250|UniProtKB:P16671};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45261;
CC Evidence={ECO:0000250|UniProtKB:P16671};
CC -!- SUBUNIT: Interacts with THBS1 and THBS2; the interactions mediate the
CC THBS antiangiogenic activity. Upon interaction with a ligand, such as
CC oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42, rapidly
CC forms a complex with TLR4 and TLR6; the complex is internalized and
CC triggers an inflammatory signal. Through its C-terminus, interacts with
CC PTK2, PXN and LYN, but not with SRC. LYN kinase activity is required
CC for facilitating TLR4:TLR6 heterodimerization and signal initiation.
CC Upon interaction with ligands such as diacylated lipopeptides,
CC interacts with the TLR2:TLR6 heterodimer (By similarity). Interacts
CC with CD9, CD81, FCER1G, ITGB2 and/or ITGB2; forming a membrane
CC heteromeric complex required for the internalization of CD36 and its
CC ligands (By similarity). {ECO:0000250|UniProtKB:P16671,
CC ECO:0000250|UniProtKB:Q08857}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P16671};
CC Multi-pass membrane protein {ECO:0000255}. Membrane raft
CC {ECO:0000250|UniProtKB:P16671}. Golgi apparatus
CC {ECO:0000250|UniProtKB:P16671}. Apical cell membrane
CC {ECO:0000250|UniProtKB:Q08857}. Note=Upon ligand-binding, internalized
CC through dynamin-dependent endocytosis. {ECO:0000250|UniProtKB:P16671}.
CC -!- PTM: Palmitoylated by ZDHHC5. Palmitoylation is required for proper
CC localization at the plasma membrane. {ECO:0000250|UniProtKB:P16671}.
CC -!- PTM: Ubiquitinated at Lys-469 and Lys-472. Ubiquitination is induced by
CC fatty acids such as oleic acid and leads to degradation by the
CC proteasome. Ubiquitination and degradation are inhibited by insulin
CC which blocks the effect of fatty acids. {ECO:0000250|UniProtKB:P16671,
CC ECO:0000250|UniProtKB:Q08857}.
CC -!- SIMILARITY: Belongs to the CD36 family. {ECO:0000305}.
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DR EMBL; U42430; AAB18646.1; -; mRNA.
DR AlphaFoldDB; P70110; -.
DR SMR; P70110; -.
DR STRING; 10036.XP_005080935.1; -.
DR eggNOG; KOG3776; Eukaryota.
DR Proteomes; UP000189706; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031526; C:brush border membrane; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:1990000; P:amyloid fibril formation; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro.
DR GO; GO:0071726; P:cellular response to diacyl bacterial lipopeptide; ISS:UniProtKB.
DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; ISS:UniProtKB.
DR GO; GO:0070508; P:cholesterol import; ISS:UniProtKB.
DR GO; GO:0097009; P:energy homeostasis; ISS:UniProtKB.
DR GO; GO:0006955; P:immune response; IEA:InterPro.
DR GO; GO:0050892; P:intestinal absorption; ISS:UniProtKB.
DR GO; GO:0030299; P:intestinal cholesterol absorption; ISS:UniProtKB.
DR GO; GO:0044539; P:long-chain fatty acid import into cell; ISS:UniProtKB.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:UniProtKB.
DR GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; ISS:UniProtKB.
DR GO; GO:0031623; P:receptor internalization; ISS:UniProtKB.
DR GO; GO:0070542; P:response to fatty acid; ISS:UniProtKB.
DR GO; GO:0070543; P:response to linoleic acid; ISS:UniProtKB.
DR GO; GO:0033993; P:response to lipid; ISS:UniProtKB.
DR GO; GO:0050909; P:sensory perception of taste; ISS:UniProtKB.
DR GO; GO:0034197; P:triglyceride transport; ISS:UniProtKB.
DR InterPro; IPR005428; CD36/SCARB1/SNMP1.
DR InterPro; IPR033076; CD36_chordates.
DR InterPro; IPR002159; CD36_fam.
DR PANTHER; PTHR11923; PTHR11923; 1.
DR PANTHER; PTHR11923:SF12; PTHR11923:SF12; 1.
DR Pfam; PF01130; CD36; 1.
DR PRINTS; PR01610; CD36ANTIGEN.
DR PRINTS; PR01609; CD36FAMILY.
PE 2: Evidence at transcript level;
KW Cell adhesion; Cell membrane; Disulfide bond; Glycoprotein;
KW Golgi apparatus; Isopeptide bond; Lipid transport; Lipoprotein; Membrane;
KW Palmitate; Receptor; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport; Ubl conjugation.
FT CHAIN 1..472
FT /note="Platelet glycoprotein 4"
FT /id="PRO_0000144152"
FT TOPO_DOM 1..7
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 8..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..439
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 440..461
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 462..472
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 93..120
FT /note="Required for interaction with thrombospondins, THBS1
FT and THBS2"
FT /evidence="ECO:0000250"
FT REGION 460..472
FT /note="Interaction with PTK2, PXN and LYN"
FT /evidence="ECO:0000250|UniProtKB:P16671"
FT SITE 463
FT /note="Critical for TLR4-TLR6 dimerization and signaling"
FT /evidence="ECO:0000250|UniProtKB:P16671"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 7
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 464
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 466
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 102
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 132
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 205
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 235
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 247
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 321
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 417
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 243..311
FT /evidence="ECO:0000250"
FT DISULFID 272..333
FT /evidence="ECO:0000250"
FT DISULFID 313..322
FT /evidence="ECO:0000250"
FT CROSSLNK 469
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P16671"
FT CROSSLNK 472
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P16671"
SQ SEQUENCE 472 AA; 52871 MW; 59948491F16C2E10 CRC64;
MGCDRNCGLI AGAVIGAVLA VFGGILMPVG DMLVEKTIKK EVVLEEGTIA FKNWVKTGTT
VYRQFWIFDV QNPDEVAVNS SKIKVKQRGP YTYRVRYLAK ENITQDPVDS TVSFVQPNGA
IFEPSLSVGT ENDTFTILNL AVAAAPHIYT NSFVQVVLNS LIKKSKSSMF QTRTLRELLW
GYKDPFLSLV PYPIPTTVGV FYPYNDTADG VYKVFNGKDD INKVAIIDSY KGKRNLSYWE
SYCDMINGTD AASFPPFVEK SRVLRFFSSD ICRSIYAVFG SDIELKGIPV YRFILPAKAF
ASPVQNPDNH CFCTEKVISN NCTSYGVLDI SKCKQGRPVY ISLPHFLHAS PDISEPIEGL
NPNEEEHRTY LDVEPITGFT LQFAKRLQVN ILVKPARKIE ALKNLKRNYI VPILWLNETG
TIGDEKAEMF RNQVTGKVKL LGLVEMVLLG LGVVMFVAFM ISYCACRSKN RK
